Costs of Risk-Based Monitoring

Are there additional costs with risk-based monitoring of clinical trials?

Money Matters: Payday again, so this topic falls under the theme of trial fiscal management. Like a steady paycheck, you can look for blog updates on financial topics in this semi-monthly series.

Are there additional costs with risk-based monitoring of clinical trials?

Clinical trials are expensive and in many case studies and presentations I (and some of my executives) have been hearing that risk-based monitoring is a potential cost-saving mechanism; that gets our attention. I have not had direct experience implementing formal targeted risk-based monitoring so today’s post will focus on the potential savings we are being promised. I have worked on studies that used centralized statistical monitoring, remote monitoring and data review, and other diverse monitoring methods; however these trials always deployed 100% Source Data Verification (SDV).

I’m intrigued by the concept of saving money by combining more data vigilance with less of the direct cost-driving SDV. At the same time, I also wonder, how will I measure the savings in my own trials? Are there hidden costs of implementation that I need to consider?

100% SDV – If it ain’t broke, don’t fix it…or is it broken?

So how did we even get here? What are the costs of risk-based monitoring? Why is 100% SDV a bad thing? Why don’t we think we should pay for it anymore? Where is this desire coming from to reduce on-site monitoring time? On-site monitoring accounts for a lot of the direct cost in clinical trials. As more tools are available to remotely monitor operations of a clinical trial, many traditional monitoring roles can now be performed without the need for frequent on-site visits. Further, some retrospective studies evaluating the impact of the SDV process report a relatively small volume of actual data changes as measured by audit trail and query activity.

Incidentally, most sponsors are already conducting varying levels of remote monitoring of data. Much of the data we capture in clinical trials is currently captured electronically and we can review it during conduct. We use central labs, ECGs, electronic patient-reported outcomes, patient profiles, listings, and other mechanisms to identify query and analyze safety signals, unusual patterns, potential errors, or unexpected results. For the activities we are already doing the cost remains constant. Where we choose to ramp up, we will be accepting additional expenses.

I plan to explore more risk-based monitoring themes in future blog posts but it takes us a bit off-topic to continue now so I’ll get back to money matters. Today let’s seek out those savings we are all waiting for in clinical trials conduct.

Let’s begin with some assumptions

First and foremost, let’s just agree that remote monitoring, partial SDV, and any other tool deployed for risk-based monitoring will not negate the need for all on-site monitoring. Our monitors will still travel to study sites although possibly less frequently and potentially not until certain pre-defined trial triggers are met. There will still be on-site visits and we will still have travel expense pass-throughs (presumably the total dollar amount will be less?).

Secondly, as Clinical Trial Managers implementing a risk-based monitoring strategy, we will continue to be as responsible as ever to our contracts/finance people, big-wigs, boards, shareholders etc. We can’t just spend wildly on the operations of a trial, nothing is changing here, if anything we will be asked to find more ways to save. We’ll need to account for any additional costs and if we do anticipate savings we will need to quantify, track them, and ensure that we defend cost-savings through the end of the project.

Finally, our partners and Contract Research Organizations (CROs) aren’t suddenly in the business of deep-discounting their service offerings just to cut the industry a break. Their margins on service offerings are just as important as ever. If we ask them to embrace risk-based monitoring methodology they will gladly accommodate our requests (and have already done so) and in turn they will rightly adjust their proposals to bid out the projects so they continue to recoup expenses and realize their desired level of profits. That’s just good sustainable business practice, and I am not criticizing or judging here but I will be asking the right questions so we budget appropriately, apply oversight, and limit future Change of Scope.

Robbing Peter to pay Paul…wait, Peter still wants to get paid!

budget

The total cost of engagement for a project may very well be less under risk-based monitoring. However, if we are spending less money for on-site monitoring, we are likely inclined to spend additional money in other service areas to substitute the appropriate level of oversight and remotely verify the safety of subjects and quality of data. Will the additional expenditures of implementing risk-based monitoring be equivalent to the savings from reduced on-site monitoring (or actually higher)? We may be spending less on the direct monitoring costs, but will some (or all?) of those resources need to be redirected to the additional remote monitoring, data management, and oversight of our trial?

Time

Measuring costs on the balance sheet seems pretty straight-forward but let’s also plan to quantify and predict any additional time that will be needed in regards to the total duration of our project. Once risk-based monitoring methods are in place, will the trial necessarily move along more quickly between milestones?

Total on-site time reduction

time marches on in a clinical trialIs there an advantage to simply having shorter monitoring visits? Rather than 2 days on-site, could a monitor meet all the objectives in half a day? The pass-throughs would look pretty similar but the billable on-site hours would be less. I have worked before as a Clinical Research Associate on trials with remote monitoring and I was able to conduct visits less frequently plus my visits were shorter. I just spent more time combing through listings and CRFs at home before and after my site visits; I was still 100% billable. Since I was fully-dedicated to the project, I’m not convinced that the sponsor saved a ton of money in this case by shifting my Site Management work to the home office rather than in the field. However, if the sponsor had used a different in-house CRA or data management person with a lower billable rate, there might have been some savings and that is an approach some CROs are offering.

Let’s measure cycle times with risk-based monitoring

The total duration of a trial is a huge cost-driver. You have to pay for all the systems to support the trial, the personnel to oversee the trial, the costs of IRB renewals and regulatory paperwork generation, etc. A trial that lasts longer costs more, so will risk-based monitoring help us reduce cycle times and overall duration of our trials?  I have some concerns that once clinical trial sites lose the frequency of visits from their dedicated on-site monitor (ideally a single point of contact) that cycle times may be negatively impacted.

Happily, site start-up times can be condensed by e-document management, which reduces a large portion of manual workload.

However, without the dedicated attention of a monitor, will enrollment rates suffer? Enrollment rates for the trials I have worked on are positively impacted by on-site visits. Will the lack of presence by an on-site monitor result in lagging enrollment and add to the total duration of my trial (effectively costing me more)?

I have personally witnessed time savings at the end of the trial in regards to a low volume of final query generation and rapid data lock as a result of a remote monitoring approach to clean-as-you-go.

As a final example, some clinical site personnel wait to perform data entry until right before a monitoring visit. If routine monitoring visits aren’t happening, will data entry get behind?  More concerning. will I obtain additional data as a result of extra SDV that I would miss with partial SDV? These again, are topics for another post.

I will plan to benchmark start-up timeframes, enrollment rates, data entry and query resolution timeframes, and other site performance metrics before implementing risk-based monitoring. if cycle times are increasing then I want to be able to measure them and make adjustments during a trial to reduce my cost exposure.

Resources

Will we have to ramp up on resources to overcome obstacles of implementing risk-based monitoring? Do we have sufficient personnel and trial management systems to implement and oversee the risk-based monitoring process. If we have to add resources, by how much will we increase our budget?

a busy office full of clinical trial managers

If I’m not fully utilizing my on-site CRAs can I expect that they will be yanked off my study and I will be saddled with the cost of training replacements?

Do we have the appropriate systems in place to remotely monitor the data for individual subjects and in aggregate?  Better tracking and review may mean less people needed to update status reports, complete spreadsheets, and prepare summaries but new or revised tracking systems will have associated implementation and maintenance costs.

Data Quality

Will our trials be more efficient?

Risk-based monitoring represents a process change and it is therefore reasonable to expect that there will be obstacles to implementation. Efficiency may take a hit initially due to a variety of activities including building/implementing technology, manually combining multiple data sources, changes to communication across various departments, etc. The initial increase in costs and time (and the resulting associated cost of adding time) should be expected and planned for accordingly.

Will risk-based monitoring be more effective?

As I study different approaches and implementations I am continually assured that risk-based monitoring can actually support higher quality of data and additional integrity. For now, I am buying the promise of increased data quality through effective risk-based monitoring. With the correct amount of pre-planning, implementation, and oversight we can complete quality clinical studies that utilize risk-based monitoring. What, do you venture, will it cost us?

Your relevant experience?

Please leave a comment here or continue the conversation with me via email or via my contact form. I’ll return to Money Matters again at the end of June. Please also let me know if there are specific financial or other topics you would like to see me blog about.

Are you interested in other relevant posts from the Money Matters series?

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About The Author

Nadia

Nadia Bracken, lead contributor to the Lead CRA blog and the ClinOps Toolkit blog, is a Clinical Program Manager in the San Francisco Bay Area.